Relative overexpression of the parathyroid hormone-related protein gene in human leiomyomas.

Relative overexpression of the parathyroid hormone-related protein gene in human leiomyomas.
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DOI:
10.1210/jcem.78.3.8126157
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发表时间:
1994-03
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
通讯作者:
E. C. Weir;D. Goad;A. Daifotis;W. Burtis;B. E. Dreyer;R. Nowak
E. C. Weir;D. Goad;A. Daifotis;W. Burtis;B. E. Dreyer;R. Nowak
中科院分区:
其他
文献类型:
--
作者:
E. C. Weir;D. Goad;A. Daifotis;W. Burtis;B. E. Dreyer;R. Nowak

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子宫平滑肌瘤或肌瘤是常见的育龄妇女,但其生物学知之甚少。pth相关蛋白(PTHrP)已经在生殖道的许多部位被发现。因此,我们检查了肌瘤是否表达PTHrP mRNA,并将其表达水平与正常肌层的表达水平进行了比较。从7例患者的肌瘤组织和相应的正常肌层制备的总RNA进行RNase保护分析。在所有病例中,肌瘤和子宫肌层组织均表达PTHrP,在7例中,有6例肌瘤中PTHrP的表达高于正常子宫肌层。4例患者培养的肌瘤细胞也比相应培养的正常子宫肌瘤细胞表达更高水平的PTHrP mRNA。采用双位点免疫放射测定法检测8例患者的组织提取物和9例患者培养细胞的条件培养基的PTHrP免疫反应性。在组织提取物和条件培养基中,肌瘤的平均PTHrP浓度明显高于正常肌层。肌瘤和子宫肌组织免疫组化染色PTHrP阳性。最后,PTHrP-(1-34)在体外诱导肌瘤细胞和子宫肌瘤细胞cAMP的剂量依赖性增加。这些发现提示PTHrP可能具有调节子宫肌瘤生理的自分泌/旁分泌功能,并可能在调节肌瘤生长或分化中发挥作用。
Uterine leiomyomas or fibroids are common among women of reproductive age, but their biology is poorly understood. The PTH-related protein (PTHrP) has been identified in a number of sites throughout the reproductive tract. We, therefore, examined whether fibroids express PTHrP mRNA and compared their level of expression with that in normal myometrium. Total RNA prepared from fibroid tissue and corresponding normal myometrium from seven patients was examined by RNase protection analysis. In all cases, fibroid and myometrial tissue expressed PTHrP, and in six of seven cases, PTHrP expression was higher in fibroids than in normal myometrium. Cultured fibroid cells from four patients also expressed higher levels of PTHrP mRNA than corresponding cultured normal myometrial cells. Tissue extracts from eight patients and conditioned medium from cultured cells from nine patients were examined for PTHrP immunoreactivity using a two-site immunoradiometric assay. In tissue extracts and conditioned medium, the mean PTHrP concentration was significantly higher in fibroids than normal myometrium. Immunohistochemical staining of fibroid and myometrial tissue was positive for PTHrP. Finally, PTHrP-(1-34) induced a dose-dependent increase in cAMP in fibroid and myometrial cells in vitro. These findings suggest that PTHrP may have an autocrine/paracrine function in regulating myometrial physiology and may play a role in regulating fibroid growth or differentiation.